"In this randomized, placebo-controlled trial testing venlafaxine and soy in men experiencing hot flashes, there was improvement in the number and severity of vasomotor symptoms in all treatment groups," the authors concluded. "This could be regression to the mean."

"This could also be due to a placebo effect related to participating in a double-blind trial. Both illustrate the necessity of including a control condition when testing therapies for hot flashes."

Hot flashes and other vasomotor symptoms occur in about 80% of men with prostate cancer treated with ADT. The symptoms may persist for years, and hot flashes, in particular, have been shown to have a negative effect on men's QOL. Complicating the problem is a lack of effective therapies, the authors noted.

Several studies have evaluated soy protein in women, and cross-cultural comparisons have shown lower rates of menopausal symptoms in women where soy is regularly consumed versus those where it is not. Isoflavones, soy constituents that have estrogenic and antiestrogenic properties, have produced mixed results in women.

"Because venlafaxine and soy have an impact on different physiologic mechanisms proposed to play a role in hot flashes, these treatments could potentially provide more relief when taken together," the authors noted.

To evaluate that potential, Vitolins and colleagues enrolled men with advanced prostate cancer treated with ADT in a phase III clinical trial. Eligible patients had four or more moderate-to-severe hot flashes daily and a life expectancy ≥9 months.

Investigators randomized the patients to one of four groups: milk protein and placebo, venlafaxine and milk protein, soy protein and placebo, or venlafaxine and soy protein. Treatment continued for 12 weeks, and the primary endpoint was the change in hot flash severity symptom score (HFSSS), defined as the number of hot flashes times severity.

Once enrolled in the study, men received a 30-day supply of assigned treatment, and they kept a daily diary of medication adherence and the number and severity of hot flashes (1=mild, 2=moderate, and 3=severe).

The study involved 120 participants, ages 46 to 91, about 80% of whom were white and were overweight or obese. The mean number of hot flashes ranged from 9 to 10 at baseline across the four treatment groups. Frequency declined in all groups and averaged about 5 across the four groups.

Severity averaged about 2.5 at baseline, declining to about 1.7 after 12 weeks.

The four treatment groups had a mean HFSSS of 21 to 22 at baseline, declining to about 9 in the milk protein/placebo and venlafaxine/milk protein groups by week 12, 11 in the venlafaxine/soy protein group, and 13.6 in the soy protein/placebo group.

The change in HFSSS from baseline to 12 weeks achieved statistical significance in all four groups (P<0.001), but the authors found no significant differences between treatment groups.

Evaluation of QOL scores showed no significant effect of venlafaxine on total score or scores for any subscales. Patients assigned to soy had significantly higher scores on emotional and functional subscales (P=0.025, P=0.041, respectively). No other significant differences were found.

All of the therapies were well tolerated, as a total of 19 adverse events were reported, none of which was definitely associated with treatment.

The trial was supported by the National Cancer Institute, National Center for Complementary and Alternative Medicine, and Physicians Pharmaceuticals.

Vitolins disclosed a relationship with Soy Connection. The other co-authors reported no relevant disclosures.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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